Double geminal C-H activation and reversible α-elimination in 2-aminopyridine iridium(III) complexes:: The role of hydrides and solvent in flattening the free energy surface

[H2Ir(OCMe2)(2)L-2]BF4 (1) (L = PPh3), a preferred catalyst for tritiation of pharmaceuticals, reacts with model substrate 2-(dimethylamino)pyridine (py-NMe2; py = 2-pyridyl) to give chelate carbene [H2Ir(py-N(Me)CH=)L-2]BF4 (2a) via cyclometalation, H-2 loss, and reversible alpha-elimination. Agostic intermediate [H2Ir(py-N(Me)CH2-H)L-2]BF4 (4a), seen by NMR, is predicted (DFT(B3PW91) computations) to give C-H oxidative addition to form the alkyl intermediate [(H)(eta(2)-H-2)Ir(py-N(Me)CH2-)L-2]BF4. Loss of H-2 leads to the fully characterized alkyl [HIr(OCMe2)(py-N(Me)CH2-)L-2]BF4 (3a(Me2CO)), which loses acetone to give alkylidene hydride 2a by rapid reversible alpha-elimination. 2a rapidly reacts with excess H-2 in d(6)-acetone to generate [H2Ir(OC(CD3)(2))(2)L-2]BF4 (1-d(12)), 3a((CD3)2CO), and py-NMe2 in a 1:1:1 ratio, showing reversibility and accounting for the selective isotope exchange catalyzed by 1. Reaction of 1 with py-N(CH2)(4) gives the fully characterized carbene 2c. A cis-L-2 carbene intermediate, cis-2c, observed by NMR, reacts with CO via retro alpha-elimination to give the alkyl 3c(CO), while the trans isomer, 2c, does not react; retro alpha-elimination thus requires the Ir-H bond to be orthogonal to the carbene plane. Consistent with experiment, computational studies show a particularly flat PE surface with activation of the agostic C-H bond giving a less stable H-2 complex, then formation of a kinetic carbene complex with cis-L, only seen experimentally for py-N(CH2)(4). Hydrides at key positions, together with gain or loss of solvent and H-2, flatten the PE (DeltaG) surfaces to allow fast catalysis.